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EC number: 204-524-2 | CAS number: 122-14-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20 April 1989 - 15 September 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
- Justification for study design:
- Standard study design according to OECD TG416
Test material
- Reference substance name:
- Fenitrothion
- EC Number:
- 204-524-2
- EC Name:
- Fenitrothion
- Cas Number:
- 122-14-5
- Molecular formula:
- C9H12NO5PS
- IUPAC Name:
- O,O-dimethyl O-3-methyl-4-nitrophenyl phosphorothioate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 60553
Purity: 94.6%,
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl: CD® (SD)BR
- Details on species / strain selection:
- Standard species/strain used for regulatory studies
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, NC, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 weeks
- Weight at study initiation: 199-257 g (M), 151-197 g (F)
- Fasting period before study: no
- Housing: group housed during the premating period, co-habitation during the mating period (1:1), indvidual during gestation and lactation (F)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 16 days
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Groups of 30 male and 30 female Crl: CD® (SD)BR rats each received fenitrothion in basal diet at concentrations of 0, 10, 40 and 120 ppm for 82-day (P1) or minimum of 88-day (F1a) pre-mating period, up to 21 days mating period, gestation and 28-day (F1a and F2) or 21-day (F1b) lactation period.
- Details on mating procedure:
- Rats were cohoused (1:1) for a maximum of 21 days; the day of mating (evidence of sperm in vaginal smear or presence of copulatory plug) was designated GD0.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Achieved concentrations, stability and homogeneity of the test material in the diet were analysed.
- Duration of treatment / exposure:
- Groups of rats were administered fenitrothion in the diet for 82-day (P1) or minimum of 88-day (F1a) pre-mating period, up to 21 days mating period, gestation and 28-day (F1a and F2) or 21-day (F1b) lactation period.
- Frequency of treatment:
- Daily / continuous in the diet
- Details on study schedule:
- The day on which evidence of mating was observed was designated as Day 0 of gestation. The day on which parturition was completed was designated as Day 1 of lactation. On Day 4 of lactation, the number of F1 pups was reduced to a maximum number of 8 per litter (4 males and 4 females, when possible). Offspring from the first mating (F1a) were maintained through weaning, then 30 animals/sex/group were selected as parental animals for the second generation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Remarks:
- Control (basal diet)
- Dose / conc.:
- 10 ppm
- Dose / conc.:
- 40 ppm
- Dose / conc.:
- 120 ppm
- No. of animals per sex per dose:
- 30
- Control animals:
- yes, plain diet
- Details on study design:
- Animals were assigned randomly to dose groups on the basis of bodyweight
- Positive control:
- Not required
Examinations
- Parental animals: Observations and examinations:
- Body weights and food consumption values for the parental animals were recorded throughout the study.
- Litter observations:
- Litter size and individual pup body weights were recorded during the lactation period.
- Postmortem examinations (parental animals):
- Complete gross necropsies were performed on all parental rats. All gross lesions and vagina, uterus/cervix, ovaries, mammary gland, pituitary gland, testis, epididymides, seminal vesicles, prostate, coagulating gland, pituitary gland and liver of each rat were examined for histopathology.
- Postmortem examinations (offspring):
- The F1a pups not selected as the second generation, F1b and F2 pups were sacrificed with carbon dioxide and examined for gross lesions at weaning.
- Statistics:
- Differences in parameters between the control and test groups were assessed using appropriate statistical techniques.
- Reproductive indices:
- Mating, fertility amd gestation indices were measured for both generations
- Offspring viability indices:
- Viability and lactation indices were measured for both generations
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs occurred for the male or female rats in the P1 generation as the result of exposure to diets containing the test substance.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Dosage-dependent, statistically significant effects on body weight gains, body weights and absolute and relative feed consumption values occurred for male and female rats given the test substance in the diet at a concentration of 120 ppm. Body weights and body weight gains were significantly affected by the 40 ppm in the F0 generation female rats during lactation.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Dosage-dependent, statistically significant effects on absolute and relative feed consumption values occurred for male and female rats given the test substance in the diet at a concentration of 120 ppm.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment-related microscopic changes were observed in any of the tissues specified for evaluation from male and female F0 rats
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- There were no test substance related effects on reproductive performance
Details on results (P0)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- During gestation, there tended to be an increase in the number of 120 ppm group F1 female rats with soft or liquid faeces and chromorrhinorrhea. During lactation, there tended to be an increase in the number of 120 ppm group F1 generation female rats with soft or liquid feces and statistically significant increases in the number of 120 ppm group F1 generation female rats with tremors occurred during lactation
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- No deaths and moribund sacrifices occurred as the results of effects of the test substance.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Dosage-dependent, statistically significant effects on body weight gains and body weights occurred for male and female rats given the test substance in the diet at a concentration of 120 ppm. Body weights and body weight gains were significantly affected by the 40 ppm F1 generation male rats during the postcohabitation period.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Dosage-dependent, statistically significant effects on absolute and relative feed consumption values occurred for male and female rats given the test substance in the diet at a concentration of 120 ppm. Absolute feed consumption values were significantly affected by the 40 ppm concentration of the test substance in the F1 generation female rats.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross lesions revealed at necropsy were considered as effects of the test substance
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment-related microscopic changes were observed in any of the tissues specified for evaluation from male and female F1 generation rats
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Details on results:
- There was no treatment-related mortality or clinical signs. Bodyweights and food consumption were reduced at 40 and 120 ppm. Fertility and reproductive parameters were unaffected by treatment. Gross necropsy did not reveal any treatmnet-related effects.
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- There were no test substance related effects on reproductive performance.
Details on results (P1)
Effect levels (P1)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
Target system / organ toxicity (P1)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The number of pups with observations related to morbidity/mortality (e.g. cold to touch, not nursing, weak) was increased at a concentration of 120 ppm
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- The 120 ppm concentration of the test substance was associated with significant increases in mortality.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The 120 ppm concentration of the test substance tended to reduce or significantly reduced pup body weights
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- no effects observed
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Details on results (F1)
Effect levels (F1)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1a
- Effect level:
- 40 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1b
- Effect level:
- 40 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The number of pups with observations related to morbidity/mortality (e.g. cold to touch, not nursing, weak) was increased in the F2 litters at a concentration of 120 ppm
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- The 120 ppm concentration of the test substance was associated with significant increases in mortality.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The 120 ppm concentration of the test substance tended to reduce or significantly reduced pup body weights.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Gross pathology findings for the offspring were considered incidental in nature and showed no relation to compound administration
- Histopathological findings:
- not examined
- Other effects:
- not examined
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Details on results (F2)
Effect levels (F2)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 40 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
Target system / organ toxicity (F2)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Mean intakes (mg/kg bw/d)
Animal |
Dosage group (ppm) |
|||||
10 |
40 |
120 |
||||
Male |
Female |
Male |
Female |
Male |
Female |
|
F0 (Premating) |
0.5 - 1.0 (0.7) |
0.6 - 1.1 (0.7) |
2.2 - 4.3 (2.7) |
2.5 - 4.3 (3.1) |
6.6 - 12.8 (8.0) |
7.8 - 13.5 (9.7)a |
Gestation (F1a) |
|
0.6 |
|
2.7 |
|
7.8 |
Lactation(F1a) |
|
1.3 |
|
5.4 |
|
15.2 |
Gestation (F1b) |
|
0.6 |
|
2.3 |
|
7.4 |
Lactation (F1b) |
|
1.1 |
|
4.5 |
|
12.0 |
F1a (Premating) |
0.7 |
0.8 |
2.8 |
3.3 |
8.8 |
11.1 |
Gestation |
|
0.7 |
|
2.7 |
|
8.6 |
Lactation |
|
1.3 |
|
4.8 |
|
14.1 |
Clinical signs (F1 parental females)
0 ppm |
10 ppm |
40 ppm |
120 ppm |
|
Gestation period |
|
|
|
|
Soft or liquid faeces |
0/ 0 |
7/ 1 |
1/ 1 |
18/ 4 |
Chromorhinorrhoea |
1/ 1 |
2/ 2 |
2/ 2 |
6/ 4 |
Lactation period |
|
|
|
|
Tremors |
0/ 0 |
0/ 0 |
0/ 0 |
43/ 6* |
Soft or liquid faeces |
25/ 4 |
52/ 8 |
73/ 6 |
65/ 10 |
*significantly different to controls (p<0.05)
Summary of pre-mating bodyweights (g) in parental animals
|
Male |
Female |
||||||
0 ppm |
10 ppm |
40 ppm |
120 ppm |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
|
F0 |
|
|
|
|
|
|
|
|
Day 1 |
231.3 |
229.2 |
231.2 |
229.6 |
178.0 |
175.1 |
173.8 |
174.8 |
Day 8 |
299.0 |
219.6 |
295.0 |
288.0** |
209.4 |
206.8 |
208.1 |
201.9 |
Day 15 |
338.0 |
331.1 |
340.0 |
330.0 |
233.7 |
230.1 |
230.2 |
221.2** |
Day 22 |
379.0 |
370.9 |
378.1 |
367.7 |
254.1 |
249.4 |
248.7 |
240.9 |
Day 29 |
414.5 |
405.8 |
415.5 |
400.5 |
273.9 |
267.5 |
267.1 |
256.8** |
Day 36 |
443.7 |
431.2 |
443.5 |
429.9 |
287.2 |
280.7 |
281.8 |
271.1 |
Day 43 |
474.8 |
457.8 |
468.4 |
455.3 |
298.0 |
289.3 |
290.8 |
281.7 |
Day 50 |
506.8 |
486.0* |
499.7 |
482.2* |
308.3 |
299.3 |
300.7 |
291.5 |
Day 57 |
523.6 |
504.7 |
517.3 |
499.4 |
320.0 |
310.4 |
311.5 |
301.6 |
Day 64 |
544.3 |
523.7 |
532.1 |
516.0** |
328.6 |
319.1 |
317.1 |
305.5** |
Day 71 |
561.1 |
538.4* |
552.5 |
533.7* |
332.7 |
322.7 |
325.1 |
311.8 |
Day 78 |
577.3 |
556.2 |
567.5 |
547.2* |
334.5 |
324.6 |
327.2 |
315.7 |
Day 82 |
583.8 |
562.2 |
572.7 |
556.1 |
341.5 |
331.9 |
332.4 |
319.4 |
Termination |
718.3 |
698.2 |
700.9 |
685.9 |
- |
- |
- |
- |
F1 |
|
|
|
|
|
|
|
|
Day 1 |
95.9 |
96.2 |
94.2 |
78.6** |
87.5 |
88.6 |
88.0 |
73.0** |
Day 8 |
160.8 |
157.3 |
156.9 |
125.0** |
136.7 |
135.1 |
135.9 |
109.5** |
Day 15 |
225.4 |
222.8 |
224.5 |
181.5** |
176.1 |
171.8 |
176.8 |
146.9** |
Day 22 |
293.3 |
287.4 |
288.9 |
244.0** |
205.7 |
198.9 |
205.0 |
176.0** |
Day 29 |
350.4 |
348.3 |
346.2 |
299.2** |
229.7 |
222.5 |
231.1 |
198.1** |
Day 36 |
408.5 |
402.6 |
400.9 |
350.9** |
256.8 |
247.7 |
254.2 |
223.1** |
Day 43 |
453.2 |
447.4 |
444.4 |
393.7** |
275.2 |
264.5 |
275.1 |
240.3** |
Day 50 |
489.2 |
483.5 |
476.9 |
427.9** |
290.5 |
277.4 |
289.0 |
255.0** |
Day 57 |
520.4 |
513.8 |
505.7 |
454.7** |
302.4 |
289.0 |
299.5 |
266.2** |
Day 64 |
548.2 |
538.3 |
529.3 |
477.9** |
312.8 |
298.6 |
309.4 |
275.2** |
Day 71 |
574.4 |
563.4 |
553.8 |
500.0** |
322.3 |
305.3* |
318.2 |
281.9** |
Day 78 |
600.2 |
584.7 |
577.0 |
518.1** |
329.6 |
313.7 |
324.5 |
288.7** |
Day 85 |
620.1 |
602.8 |
593.1 |
533.6** |
337.6 |
321.1 |
331.4 |
295.3** |
Termination |
800.6 |
762.9 |
744.5* |
666.1** |
- |
- |
- |
- |
*significantly different to controls (p<0.05); **p<0.01
Summary of female bodyweights during gestation and lactation
Dose level |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
F0 - First gestation |
||||
Day 0 |
338.9 |
329.8 |
322.8 |
314.6 |
Day 6 |
366.2 |
352.6 |
353.3 |
334.6 |
Day 12 |
397.6 |
386.2 |
381.8 |
364.1** |
Day 15 |
399.0 |
393.4 |
389.6 |
372.9 |
Day 20 |
464.3 |
453.9 |
448.0 |
417.6** |
F0 - Second gestation |
||||
Day 0 |
377.6 |
367.7 |
372.9 |
347.0 |
Day 6 |
401.2 |
392.3 |
397.4 |
374.2 |
Day 12 |
426.7 |
418.8 |
421.6 |
400.4 |
Day 15 |
443.6 |
433.9 |
431.9 |
412.5 |
Day 20 |
508.3 |
502.2 |
493.2 |
469.6 |
F1 - gestation |
||||
Day 0 |
346.6 |
339.5 |
338.1 |
306.1** |
Day 6 |
370.1 |
363.9 |
359.8 |
322.4** |
Day 12 |
393.1 |
389.1 |
385.1 |
347.4** |
Day 15 |
407.6 |
403.0 |
401.0 |
361.0** |
Day 20 |
475.0 |
472.5 |
466.3 |
416.9** |
Dose level |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
F0 – first lactation |
||||
Day 1 |
365.7 |
362.6 |
357.0 |
343.4 |
Day 4 |
365.7 |
357.3 |
355.5 |
329.9 |
Day 7 |
366.6 |
363.2 |
356.9 |
326.9** |
Day 10 |
384.3 |
377.0 |
368.7 |
334.2** |
Day 14 |
378.9 |
370.4 |
367.3 |
342.8** |
Day 16 |
388.3 |
380.0 |
368.4* |
346.4** |
Day 18 |
378.1 |
366.3 |
361.4 |
340.4** |
Day 21 |
368.2 |
351.9 |
349.5* |
329.1** |
Day 28 |
351.8 |
344.8 |
338.5 |
325.3 |
F0 – second lactation |
||||
Day 1 |
408.6 |
402.5 |
406.0 |
386.1 |
Day 4 |
409.0 |
403.6 |
398.2 |
378.0 |
Day 7 |
402.8 |
389.4 |
392.6 |
369.5 |
Day 10 |
410.6 |
400.6 |
405.1 |
371.7 |
Day 14 |
410.8 |
400.0 |
399.1 |
368.4** |
Day 16 |
411.6 |
411.3 |
402.6 |
373.7 |
Day 18 |
406.7 |
405.3 |
389.8 |
368.1** |
Day 21 |
391.4 |
385.8 |
379.6 |
367.0 |
F1 – lactation |
||||
Day 1 |
387.5 |
372.7 |
374.4 |
333.0** |
Day 4 |
390.2 |
367.0 |
370.6 |
320.4** |
Day 7 |
388.0 |
369.3 |
372.0 |
319.1** |
Day 10 |
398.9 |
376.9 |
375.4* |
325.9** |
Day 14 |
402.3 |
382.0 |
376.1* |
329.2** |
Day 16 |
405.7 |
389.6 |
383.7 |
339.0** |
Day 18 |
396.9 |
386.2 |
380.0 |
339.2** |
Day 21 |
394.4 |
373.5* |
370.7* |
340.1** |
Day 28 |
370.0 |
348.9* |
358.7 |
328.8** |
*significantly different to controls (p<0.05); **p<0.01
Summary of pre-mating food consumption
|
Male |
Female |
||||||
0 ppm |
10 ppm |
40 ppm |
120 ppm |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
|
F0 |
||||||||
Day 1-8 |
27.0 |
26.2 |
28.4 |
27.6 |
22.4 |
20.4** |
20.5** |
20.5** |
Day 8-15 |
29.3 |
29.8 |
29.8 |
29.1 |
24.0 |
22.9 |
23.0 |
23.7 |
Day 15-22 |
26.6 |
26.0 |
26.9 |
25.7 |
21.3 |
20.2 |
21.3 |
22.2 |
Day 22-29 |
27.6 |
27.1 |
27.4 |
26.5 |
22.0 |
20.8 |
21.1 |
20.8 |
Day 29-36 |
28.2 |
26.5 |
27.8 |
27.2 |
22.0 |
21.3 |
21.5 |
21.6 |
Day 36-43 |
28.0 |
27.2 |
27.6 |
27.2 |
21.8 |
20.2 |
20.6 |
21.1 |
Day 43-50 |
28.0 |
26.7 |
27.6 |
26.7 |
21.4 |
19.9 |
20.3 |
20.6 |
Day 50-57 |
28.0 |
27.4 |
27.8 |
27.2 |
21.0 |
19.5 |
20.0 |
19.7 |
Day 57-64 |
28.6 |
27.8 |
28.7 |
28.2 |
21.1 |
20.0 |
20.7 |
20.4 |
Day 64-71 |
28.8 |
28.4 |
29.1 |
27.7 |
21.8 |
20.3 |
21.0 |
20.0 |
Day 71-78 |
29.6 |
28.8 |
29.4 |
28.6 |
22.1 |
20.7 |
21.3 |
20.7 |
Day 78-82 |
31.5 |
31.0 |
31.3 |
30.2 |
22.2 |
20.3 |
20.8 |
20.6* |
F1 |
||||||||
Day 1-8 |
17.7 |
17.2 |
17.6 |
15.1** |
15.5 |
15.0 |
15.7 |
13.9* |
Day 8-15 |
24.6 |
24.2 |
25.1 |
21.5** |
19.8 |
19.0 |
20.1 |
18.6 |
Day 15-22 |
28.0 |
27.8 |
28.3 |
25.4* |
20.8 |
19.5* |
20.6 |
20.8 |
Day 22-29 |
30.4 |
30.3 |
31.1 |
28.1* |
21.8 |
20.5 |
22.1 |
22.1 |
Day 29-36 |
32.4 |
31.6 |
32.4 |
29.9** |
23.0 |
22.0 |
22.1 |
22.0 |
Day 36-43 |
32.4 |
32.3 |
32.6 |
29.8** |
23.2 |
21.7 |
23.1 |
22.4 |
Day 43-50 |
32.4 |
32.4 |
32.3 |
29.7** |
23.2 |
22.0 |
22.7 |
22.6 |
Day 50-57 |
32.1 |
32.0 |
32.0 |
29.3** |
23.4 |
21.4* |
21.8* |
22.1 |
Day 57-64 |
32.6 |
32.2 |
32.1 |
29.0** |
23.3 |
21.6 |
22.2 |
21.5 |
Day 64-71 |
32.3 |
31.8 |
31.3 |
28.7** |
23.2 |
20.9** |
21.5* |
20.8* |
Day 71-78 |
33.0 |
32.2 |
32.0 |
28.6** |
22.8 |
21.4 |
21.1** |
21.1 |
Day 78-85 |
34.2 |
33.1 |
33.8 |
30.1** |
24.1 |
22.9 |
22.8 |
22.8 |
*significantly different to controls (p<0.05); **p<0.01
Summary of food consumption in females during gestation and lactation
Dose level |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
F0 – first gestation |
||||
Day 0-6 |
26.3 |
23.5* |
25.6 |
22.7** |
Day 6-12 |
27.9 |
26.7 |
26.9 |
26.0 |
Day 12-15 |
23.7 |
22.3 |
24.9 |
25.2 |
Day 15-20 |
26.7 |
26.1 |
25.8 |
23.1 |
F0 - second gestation |
||||
Day 0-6 |
24.5 |
24.1 |
23.2 |
24.0 |
Day 6-12 |
26.1 |
25.4 |
24.8 |
25.4 |
Day 12-15 |
26.9 |
25.9 |
24.6 |
25.8 |
Day 15-20 |
24.4 |
24.2 |
24.6 |
24.7 |
F1 - gestation |
||||
Day 0-6 |
25.8 |
25.6 |
24.4 |
22.7 |
Day 6-12 |
27.3 |
27.2 |
26.5 |
26.0 |
Day 12-15 |
28.6 |
29.2 |
28.4 |
26.5 |
Day 15-20 |
27.8 |
28.8 |
28.3 |
25.7 |
F0 f -first lactation |
||||
Day 1-4 |
34.3 |
38.0 |
35.3 |
32.0 |
Day 4-7 |
43.6 |
40.7 |
44.7 |
43.0 |
Day 7-10 |
54.8 |
53.8 |
54.6 |
41.9** |
Day 10-14 |
62.4 |
61.0 |
60.1 |
53.6 |
F0 - second lactation |
||||
Day 1-4 |
30.0 |
28.2 |
31.3 |
24.7 |
Day 4-7 |
37.0 |
37.8 |
39.9 |
30.9** |
Day 7-10 |
49.1 |
50.1 |
49.2 |
41.8** |
Day 10-14 |
54.8 |
55.4 |
55.0 |
47.8 |
F1 - lactation |
||||
Day 1-4 |
30.2 |
28.9 |
28.1 |
23.6 |
Day 4-7 |
44.5 |
41.7 |
39.0 |
31.0** |
Day 7-10 |
55.2 |
50.9 |
48.3** |
39.6** |
Day 10-14 |
65.4 |
61.7 |
56.8** |
51.9** |
*significantly different to controls (p<0.05); **p<0.01
Summary of reproductive parameters (F1a litters)
Dose level |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
Parental reproduction indices |
||||
Total No. of males placed with females |
30 |
30 |
30 |
30 |
Total No. of males mated with females |
27 |
27 |
26 |
25 |
Total No. of mated males resulting in pregnancy |
25 |
19 |
17 |
19 |
Male mating index (%) |
90.0 |
90.0 |
86.7 |
83.3 |
Male fertility index (%) |
83.3 |
63.3 |
56.7 |
63.3 |
Total No. of females placed with males |
30 |
30 |
30 |
30 |
Total No. of females showing evidence of mating |
28 |
29 |
29 |
29 |
Total No. of females pregnant |
26 |
20 |
19 |
21 |
Female mating index (%) |
93.3 |
96.7 |
96.7 |
96.7 |
Pregnancy rate (%) |
92.8 |
69.0 |
65.5 |
72.4 |
No. of females delivering offspring |
26 |
19a |
19 |
21 |
No. of females delivering viable offspring |
26 |
19 |
19 |
21 |
Parturition index (%) |
100 |
100 |
100 |
100 |
Offspring indices |
||||
Mean No. of live pups at parturition/litter |
14.6 |
14.6 |
12.8 |
12.2 |
Mean No. of stillborn/litter |
0.2 |
0.0 |
0.2 |
0.3 |
Viability index (%) |
96.8 |
99.3 |
98.4 |
86.0** |
Lactation index (%) |
99.0 |
100.0 |
100.0 |
91.5** |
Number of surviving pups/litter |
||||
Day 1 |
14.6 |
14.6 |
12.8 |
12.2 |
Day 4 (pre-cull) |
14.1 |
14.5 |
12.6 |
10.5* |
Day 4 (post-cull) |
8.0 |
7.7 |
7.7 |
6.7* |
Day 7 |
8.0 |
7.7 |
7.7 |
6.3* |
Day 14 |
7.9 |
7.7 |
7.7 |
6.2* |
Day 21 |
7.9 |
7.7 |
7.7 |
6.2* |
Day 28 |
7.9 |
7.7 |
7.7 |
6.1** |
Mean pup weight/litter (g) |
||||
Day 1 |
6.5 |
6.5 |
6.8 |
6.2 |
Day 4 (pre-cull) |
9.8 |
9.5 |
10.0 |
8.8 |
Day 4 (post-cull) |
9.8 |
9.5 |
10.2 |
8.9 |
Day 7 |
16.5 |
15.8 |
16.8 |
13.8 |
Day 14 |
35.2 |
34.9 |
35.4 |
28.7** |
Day 21 |
55.0 |
54.3 |
54.1 |
45.9** |
Percent male pups (%) |
||||
Day 1 |
45.5 |
51.0 |
49.2 |
53.9 |
Day 4 (pre-cull) |
45.0 |
51.4 |
48.8 |
53.0 |
Day 4 (post-cull) |
49.0 |
48.0 |
49.6 |
53.2 |
Day 7 |
49.3 |
48.0 |
49.6 |
53.0 |
Day 14 |
49.0 |
48.0 |
49.6 |
53.0 |
Day 21 |
49.0 |
48.0 |
49.6 |
53.0 |
Day 28 |
49.0 |
48.0 |
49.6 |
52.6 |
*significantly different to controls (p<0.05); **p<0.01
Summary of reproductive parameters (F1b litters)
Dose level |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
Parental reproduction indices |
||||
Total No. of males placed with females |
30 |
28a |
30 |
30 |
Total No. of males mated with females |
25 |
23 |
23 |
17* |
Total No. of mated males resulting in pregnancy |
22 |
18 |
17 |
14 |
Male mating index (%) |
83.3 |
82.1 |
76.7 |
56.7* |
Male fertility index (%) |
73.3 |
64.3 |
56.7 |
46.7 |
Total No. of females placed with males |
30 |
28 |
30 |
30 |
Total No. of females showing evidence of mating |
27 |
25 |
25 |
20 |
Total No. of females pregnant |
24 |
19 |
18 |
16 |
Female mating index (%) |
90.0 |
89.3 |
83.3 |
66.7 |
Pregnancy rate (%) |
88.9 |
76.0 |
72.0 |
80.0 |
No. of females delivering offspring |
24 |
19 |
17 |
14b |
No. of females delivering viable offspring |
24 |
19 |
16c |
14 |
Parturition index (%) |
100.0 |
100.0 |
94.1 |
100.0 |
Offspring indices |
||||
Mean No. of live pups at parturition/litter |
14.4 |
15.1 |
12.7 |
12.3 |
Mean No. of stillborn/litter |
0.1 |
0.4 |
0.3 |
0.0 |
Viability index (%) |
96.8 |
98.6 |
98.0 |
97.7 |
Lactation index (%) |
100.0 |
94.7** |
100.0 |
96.3* |
Number of surviving pups/litter |
|
|
|
|
Day 1 |
14.4 |
15.1 |
12.7 |
12.3 |
Day 4 (precull) |
14.0 |
14.9 |
12.4 |
12.0 |
Day 4 (postcull) |
7.7 |
8.0 |
7.5 |
7.6 |
Day 7 |
7.7 |
8.0 |
7.5 |
7.5 |
Day 14 |
7.7 |
8.0 |
7.5 |
7.4 |
Day 21 |
7.7 |
8.0 |
7.5 |
7.4 |
Mean pup weight/litter (g) |
||||
Day 1 |
6.7 |
6.5 |
6.8 |
6.5 |
Day 4 (precull) |
10.2 |
9.6 |
10.8 |
9.7 |
Day 4 (postcull) |
10.3 |
9.6 |
10.9 |
9.8 |
Day 7 |
17.0 |
16.0 |
17.9 |
14.6 |
Day 14 |
36.6 |
34.8 |
37.9 |
29.6** |
Day 21 |
56.2 |
55.3 |
57.9 |
47.6** |
Percent male pups (%) |
||||
Day 1 |
51.1 |
48.1 |
47.3 |
47.1 |
Day 4 (precull) |
52.1 |
48.2 |
46.3 |
47.9 |
Day 4 (postcull) |
51.4 |
48.7 |
48.4 |
48.6 |
Day 7 |
51.4 |
48.7 |
48.4 |
48.6 |
Day 14 |
51.4 |
48.7 |
48.4 |
49.6 |
Day 21 |
51.4 |
48.6 |
48.4 |
49.6 |
*significantly different to controls (p<0.05); **p<0.01
Summary of reproductive parameters (F2 litters)
Dose level |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
Parental reproduction indices |
||||
Total No. of males placed with females |
29a |
30 |
30 |
30 |
Total No. of males mated with females |
24 |
24 |
22 |
21 |
Total No. of mated males resulting in pregnancy |
18 |
21 |
21 |
17 |
Male mating index (%) |
82.8 |
80.0 |
73.3 |
70.0 |
Male fertility index (%) |
62.1 |
70.0 |
70.0 |
56.7 |
Total No. of females placed with males |
29b |
30 |
30 |
30 |
Total No. of females showing evidence of mating |
27 |
27 |
26 |
28 |
Total No. of females pregnant |
19 |
23 |
24 |
21 |
Female mating index (%) |
93.1 |
90.0 |
86.7 |
93.3 |
Pregnancy rate (%) |
70.4 |
85.2 |
92.3 |
75.0 |
No. of females delivering offspring |
18c |
23 |
24 |
20d |
No. of females delivering viable offspring |
18 |
23 |
24 |
20 |
Parturition index (%) |
100 |
100 |
100 |
100 |
Offspring indices |
||||
Mean No. of live pups at parturition/litter |
13.6 |
13.7 |
13.0 |
12.4 |
Mean No. of stillborn/litter |
0.2 |
0.2 |
0.1 |
0.2 |
Viability index (%) |
99.6 |
99.0 |
99.7 |
85.5** |
Lactation index (%) |
100.0 |
100.0 |
99.4 |
89.8** |
Number of surviving pups/litter |
||||
Day 1 |
13.6 |
13.7 |
13.0 |
12.4 |
Day 4 (precull) |
13.6 |
13.6 |
13.0 |
10.6 |
Day 4 (postcull) |
8.0 |
7.9 |
7.4 |
6.8 |
Day 7 |
8.0 |
7.9 |
7.4 |
6.6* |
Day 14 |
8.0 |
7.9 |
7.4 |
6.2* |
Day 21 |
8.0 |
7.9 |
7.4 |
6.2* |
Day 28 |
8.0 |
7.9 |
7.4 |
6.2* |
Mean pup weight/litter (g) |
||||
Day 1 |
6.8 |
6.7 |
6.6 |
6.5 |
Day 4 (precull) |
10.4 |
9.9 |
9.6 |
8.4** |
Day 4 (postcull) |
10.4 |
10.0 |
9.6 |
8.4* |
Day 7 |
17.0 |
16.5 |
15.8 |
12.1** |
Day 14 |
36.4 |
35.0 |
34.0 |
26.8** |
Day 21 |
58.2 |
56.2 |
54.4 |
44.0** |
Percent male pups (%) |
||||
Day 1 |
46.5 |
49.2 |
50.0 |
56.4 |
Day 4 (precull) |
46.7 |
49.3 |
50.0 |
57.2 |
Day 4 (postcull) |
48.6 |
49.6 |
50.3 |
54.9 |
Day 7 |
48.6 |
49.6 |
50.3 |
54.2 |
Day 14 |
48.6 |
49.6 |
50.3 |
57.4 |
Day 21 |
48.6 |
49.6 |
50.6 |
57.4 |
Day 28 |
48.6 |
49.6 |
50.6 |
57.4 |
Summary of litter observations
|
F1a |
F2 |
||||||
0 ppm |
10 ppm |
40 ppm |
120 ppm |
0 ppm |
10 ppm |
40 ppm |
120 ppm |
|
Litters examined (N) |
26 |
19 |
19 |
21 |
18 |
23 |
24 |
20 |
Small and weak |
2/2 |
0/0 |
0/0 |
14/5 |
0/0 |
0/0 |
0/0 |
0/0 |
Thin appearance |
0/0 |
0/0 |
0/0 |
3/1 |
0/0 |
0/0 |
0/0 |
0/0 |
Weak |
0/0 |
0/0 |
0/0 |
22/2 |
0/0 |
0/0 |
0/0 |
21/3 |
Cold to touch |
0/0 |
2/1 |
17/2 |
61/4 |
0/0 |
0/0 |
5/2 |
56/4 |
Pup not nursing |
1/1 |
0/0 |
0/0 |
14/3 |
0/0 |
0/0 |
0/0 |
53/3 |
Pale appearance |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
22/3 |
White substance surrounding umbilicus |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
0/0 |
1/1 |
Tremors |
0/0 |
0/0 |
0/0 |
2/1 |
0/0 |
0/0 |
1/1 |
0/0 |
Urine-stained abdominal fur |
0/0 |
0/0 |
0/0 |
1/1 |
0/0 |
0/0 |
0/0 |
0/0 |
Lesion |
0/0 |
0/0 |
0/0 |
4/2c |
0/0 |
0/0 |
0/0 |
11/1 |
Bite wound |
0/0 |
0/0 |
0/0 |
2/1 |
0/0 |
0/0 |
2/1b |
11/1 |
Right front leg and paw missing |
0/0 |
0/0 |
0/0 |
3/1 |
0/0 |
0/0 |
0/0 |
0/0 |
Tail missing |
0/0 |
0/0 |
29/2 |
3/1 |
0/0 |
0/0 |
4/1 |
25/1 |
Back discolored |
0/0 |
0/0 |
0/0 |
2/1 |
0/0 |
0/0 |
0/0 |
0/0 |
Mouth discolored |
2/1 |
0/0 |
0/0 |
2/1 |
0/0 |
0/0 |
0/0 |
0/0 |
Applicant's summary and conclusion
- Conclusions:
- No effects on fertililty or reproductive capacity were seen in this study at dose levels sufficient to cause general toxicity in parental rats and offspring. In the absence of any effects, a reproductive NOAEL of 120 ppm (7.4-15.2 mg/kg bw/d) can be determined for this study. A parental NOAEL of 10 ppm (0.7 mg/kg bw/d) can be determined, based on bodyweight effects at higher dose levels. An offspring NOAEL of 40 ppm (2.3-5.4 mg/kg bw/d) can be determined for this study, based on increased mortality and bodyweight effects at the highest dose level.
- Executive summary:
A two-generation reproductive toxicity study was performed in the rat uisng dietary concentrations of fenitrothion of 0, 10, 40 and 120 ppm. Successive generations of rats were exposed for at least 10 weeks prior to mating and throughout mating, gestation and lactation of the tresulting litters. The first generation was mated to produce two litters. Adminstration of the highest dose level resulted in clinical signs, reduced food consumption and bodyweight effects in parental animals. Bodyweight effects were also apparent in parental animals at 40 ppm. There were no effects on fertility in either generation. Increased pup mortality, clinical signs and reduced weight gain were seen in pups of both generations at 120 ppm. No effects on fertililty or reproductive capacity were seen in this study at dose levels sufficient to cause general toxicity in parental rats and offspring. In the absence of any effects, a reproductive NOAEL of 120 ppm (7.4-15.2 mg/kg bw/d) can be determined for this study. A parental NOAEL of 10 ppm (0.7 mg/kg bw/d) can be determined, based on bodyweight effects at higher dose levels. An offspring NOAEL of 40 ppm (2.3-5.4 mg/kg bw/d) can be determined for this study, based on increased mortality and bodyweight effects at the highest dose level.
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